Computational modeling of the postsynaptic mechanisms of the dopaminergic and glutamatergic integration in a hippocampal dendritic spine in health and pathological conditions

• Grant number: 14/08481-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): July 01, 2014
• Effective date (End): June 30, 2017
• Field of knowledge: Biological Sciences - Biophysics
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Antonio Carlos Roque da Silva Filho
• Grantee: Gabriela Antunes
• Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In hippocampal neurons, the action of dopamine on the glutamatergic transmission modulates the synaptic long-term potentiation (LTP) and depression (LTD) and, consequently, the occurrence of learning and memory. Alterations of the dopaminergic and glutamatergic integration in the hippocampus are putative candidates to act as the molecular basis for the cognitive symptoms of several pathologies. However, the dynamics of the molecular mechanisms involved in this integration remains poorly understood. Thus, the aim of this proposal is to develop a computational model of a hipocampal dendritic spine containing the glutamatergic and dopaminergic synaptic receptors, their respective signaling pathways and integration mechanisms during health and pathological conditions. This model will unify the experimental information available in the literature to simulate the action of dopamine on the glutamatergic transmission during the occurrence of LTP and LTD. Subsequently, physiological alterations associated with two pathological processes, the Parkinson disease and schizophrenia, will be implemented in the model. The physiological alterations associated with these pathologies impair the occurrence of the hipocampal LTP and LTD and will be simulated systematically to verify their consequences on the model dynamics. These simulations will be used to indicate modifications in the components of the model that can rescue its health condition in an attempt to find new therapeutic targets. It is expected that the results of this work will give insights on the molecular aspects of the synaptic plasticity in health conditions and during the investigated pathologies, and will help in the identification of new therapeutic targets to treat them. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANTUNES, G.; SIMOES-DE-SOUZA, F. M. AMPA receptor trafficking and its role in heterosynaptic plasticity. SCIENTIFIC REPORTS, v. 8, JUL 9 2018. Web of Science Citations: 2.

ANTUNES, GABRIELA; FARIA DA SILVA, SAMUEL F.; SIMOES DE SOUZA, FABIO M. Mirror Neurons Modeled Through Spike-Timing-Dependent Plasticity are Affected by Channelopathies Associated with Autism Spectrum Disorder. International Journal of Neural Systems, v. 28, n. 5, SI JUN 2018. Web of Science Citations: 6.

ANTUNES, G.; ROQUE, A. C.; SIMOES-DE-SOUZA, F. M. Molecular mechanisms of detection and discrimination of dynamic signals. SCIENTIFIC REPORTS, v. 8, FEB 6 2018. Web of Science Citations: 1.

ANTUNES, G.; ROQUE, A. C.; SIMOES-DE-SOUZA, F. M. Stochastic Induction of Long-Term Potentiation and Long-Term Depression. SCIENTIFIC REPORTS, v. 6, AUG 3 2016. Web of Science Citations: 4.

ANTUNES, GABRIELA; ROQUE, ANTONIO C.; SIMOES DE SOUZA, FABIO M. Modelling intracellular competition for calcium: kinetic and thermodynamic control of different molecular modes of signal decoding. SCIENTIFIC REPORTS, v. 6, APR 1 2016. Web of Science Citations: 10.